Lafora Disease during a Seven-Year Period, Bosnian and Herzegovinian experience

Lafora progressive myoclonus epilepsy (Lafora disease, LD) is a fatal autosomal recessive neurodegenerative disorder (with an onset in teenage years in previously normal adolescents). This paper represents a view of a patient diagnosed with Lafora progressive myoclonus epilepsy, over a course of seven years. A description of the initial manifestation of symptoms, doctors' attempts to combat the symptoms with drug treatment, further attempts towards reaching the correct diagnosis, the final confirmation of the Lafora diagnosis (mutation in the NHLRC1 gene), and the current state of the patient is presented. The absence of a positive family history, the lack of staff specialized in dealing with this or similar pathology, and the diagnostic inability to characterize this type of disorder in Bosnia and Herzegovina have led to a fair delay in diagnosing and beginning of an adequate pharmacological treatment. Overall, recent identification of LD cases in Bosnia and Herzegovina warrants an establishment of a Centre for Genetic Testing in order to ensure more humane counseling of an entire family whose family member(s) might be diagnosed with this devastating and currently an incurable disorder.


Introduction
This paper represents a view of a patient diagnosed with Lafora progressive myoclonus epilepsy (Lafora disease, LD), over a seven-year-long period, including the beginning of symptoms, the attempts to combat the symptoms with drug treatment, the attempts at reaching the correct diagnosis, the confirmation of the diagnosis (mutation in the NHLRC1 gene), and the current state of the patient. Parents as legal representative signed informed consent. Local ethical approval for case presentation was obtained.

Case report
In Apr 2008, a 9-yr-old girl with initials A.S. (born in 1999, in Maglaj, Bosnia and Herzegovina) was admitted into the General Hospital Tesanj (Tesanj, Bosnia and Herzegovina) with a severe headache, mental confusion, high fever, and a cough. Neither the patient's own medical history nor that of her family contained details of any specific disorder.
Both her birth weight (3850 gr) and her birth length (58 cm) were considered normal. Prior to that admission to the hospital, she manifested no cognitive disabilities. She was diagnosed with having epilepsy with mental disorientation and she was treated with phenobarbitone, sodium valproate, and lamotrigine. Then, in 2010, she started having seizures: they would begin with nausea, impaired vision, and a loss of consciousness. During the seizures, her eyes were tightly closed and she exhibited no twitching of her legs nor her arms.
After ten to thirty min, the patient would regain consciousness and would complain of feeling cold at the terminal part of extremities. Additionally, she would feel pain in her ankles, with bruising joints, after which the pain would progress towards her toes, followed by swelling and reddening.
Magnetic resonance imaging (MRI) of the patient's head showed no apparent changes in the structure of the patient's brain.
During the third year following the onset of her symptoms and her first seizure, the patient experienced a different type of "seizure" during her sports class: she began to walk aimlessly and insecurely, with tottering, she had a fixed gaze, pale face, and was rambling (calling a friend by her name over and over again). However, she did not lose her balance and did not fall. In addition, she manifested no twitching of extremities. That particular "seizure" lasted for about ten minutes, after which she regained consciousness. However, following that particular seizure the patient failed to re-establish her previous state: she had absent gaze, difficulty using cutlery, she lost her sense in space and time, and she did not recognize her parents and people she previously knew around her.

In Conclusion
LD is a rare progressive myoclonus epilepsy, with a very uncertain and poor prognosis, and only treatment of symptoms can be carried out, and it requires a multidisciplinary approach in the treatment and understanding of the overall community. Recent identification of LD cases in Bosnia and Herzegovina warrants an establishment of a Centre for Genetic Testing in order to ensure more humane counseling of an entire family whose family member(s) might be diagnosed with this devastating and currently an incurable disorder.

Acknowledgement
We thank Smail Zubcevic, MD, PhD for comments that greatly improved the manuscript.

Authors' Contribution
Edin Begic gave substantial contributions to the conception and design of the work and the acquisition, analysis and interpretation of data for the work. Each author was included in drafting of the work and revised it critically for important intellectual content and gave final approval of the version to be published. Each author made agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved